The development of problem behavior in children is associated with exposure to environmental factors, including the maternal environment. Both are influenced by genetic factors, which may also be correlated, that is, environmental risk and problem behavior in children might be influenced by partly the same genetic factors. In addition, environmental and genetic factors could interact with each other increasing the risk of problem behavior in children. To date, limited research investigated these mechanisms in a genome-wide approach. Therefore, the goal of this study was to investigate the association between genetic risk for psychiatric and related traits, as indicated by polygenetic risk scores (PRSs), exposure to previously identified maternal risk factors, and problem behavior in a sample of 1,154 children from the Amsterdam Born Children and their Development study at ages 5–6 and 11–12 years old. The PRSs were derived from genome-wide association studies (GWASs) on schizophrenia, major depressive disorder, neuroticism, and wellbeing. Regression analysis showed that the PRSs were associated with exposure to multiple environmental risk factors, suggesting passive gene–environment correlation. In addition, the PRS based on the schizophrenia GWAS was associated with externalizing behavior problems in children at age 5–6. We did not find any association with problem behavior for the other PRSs. Our results indicate that genetic predispositions for psychiatric disorders and wellbeing are associated with early environmental risk factors for children's problem behavior.

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Keywords children, early life stress, gene–environment correlation, gene–environment interaction, psychopathology
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Journal American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
Ensink, J.B.M. (Judith B. M.), de Moor, M.H.M. (Marleen H. M.), Zafarmand, M.H, de Laat, S. (Sanne), Uitterlinden, A. (André), Vrijkotte, T.G.M, … Middeldorp, C.M. (2019). Maternal environmental risk factors and the development of internalizing and externalizing problems in childhood: The complex role of genetic factors. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics. doi:10.1002/ajmg.b.32755